2. Academic Validation
  3. Structural Insight into TNIK Inhibition

Structural Insight into TNIK Inhibition

  • Int J Mol Sci. 2022 Oct 27;23(21):13010. doi: 10.3390/ijms232113010.
Mutsuko Kukimoto-Niino 1,  Mikako Shirouzu 1,  Tesshi Yamada 2
Affiliations

Affiliations

  • 1 Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
  • 2 Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
PMID: 36361804 DOI: 10.3390/ijms232113010
Abstract

TRAF2- and NCK-interacting kinase (TNIK) has emerged as a promising therapeutic target for colorectal Cancer because of its essential role in regulating the Wnt/β-catenin signaling pathway. Colorectal cancers contain many mutations in the Wnt/β-catenin signaling pathway genes upstream of TNIK, such as the adenomatous polyposis coli (APC) tumor suppressor gene. TNIK is a regulatory component of the transcriptional complex composed of β-catenin and T-cell factor 4 (TCF4). Inhibition of TNIK is expected to block the aberrant Wnt/β-catenin signaling caused by colorectal Cancer mutations. Here we present structural insights into TNIK inhibitors targeting the ATP-binding site. We will discuss the effects of the binding of different chemical scaffolds of nanomolar inhibitors on the structure and function of TNIK.

Keywords

APC; TCF4; TNIK; Wnt signaling; colorectal cancer; inhibitor; β-catenin.

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